PROJECT SUMMARY/ ABSTRACT Repetitive head impacts (RHI) sustained in contact sports is a growing public health issue. Even though RHI may not cause an observable brain injury with conventional imaging techniques, growing evidence indicates that if sustained repetitively, subconcussive low levels of head impact can cause significant head injury and increase the concussion susceptibility. Still, identification of individuals who sustain RHI-induced injury is challenging as they are often asymptomatic when evaluated with current diagnostics. An urgent need exists to develop new assessment tools that detect progressive subtle changes from minor, but repeated impacts to identify RHI-induced injury in its asymptomatic state. While subconcussive, RHI may be a sufficient trauma load to disrupt the brain?s protective membrane system (i.e., pia-arachnoid complex, or PAC) and progressively degrade its protective function, placing the individual vulnerable to future injury. Although invisible with current imaging modalities, our hypothesis is PAC functional status can be detected by assessing skull-brain (SB) decoupling performance modulated by the PAC, and individuals who have previously experienced RHI will have changes in SB decoupling performance compared with normal volunteers with no history of RHI, presumably reflecting the PAC degradation following RHI. Currently, a noninvasive tool to quantify SB decoupling performance and its potential degradation following RHI does not exist. Our goals are to (1) develop and explore novel magnetic resonance elastography (MRE)-based techniques for quantifying SB mechanical decoupling performance and (2) establish new quantitative biomarkers assessing the RHI-induced injury to the PAC in humans. In Aim 1, we will develop a new MRE-based imaging technique to quantify the dynamic mechanical coupling parameters of the SB interface under various loading conditions. This new system will integrate a multi-excitation head driver system inducing the desired various mechanical stimuli (including changes in vibration frequency/direction/preload), a pulse sequence estimating corresponding full-volume 3D SB displacement fields, and a post-processing approach assessing resultant SB coupling parameters in vivo. This will create a foundation to characterize the PAC?s transmissibility, connectivity, transmission coefficients, directional variation, and loading sensitivity, possibly distinguishing between a healthy PAC and a PAC with degraded function. In Aim 2, we will evaluate the repeatability and reproducibility of the MRE-assessed SB coupling parameters in healthy volunteers using a test-retest strategy. A pilot clinical study will also be performed to evaluate and compare MRE-assessed SB coupling parameters in age-/sex-matched normal and RHI participants. Taken together, these aims will provide innovative methods and unique datasets for studying SB biomechanics, and novel imaging biomarkers to aid clinicians in identifying individuals who have sustained the RHI-induced injury to the PAC. More broadly, this project will expand our understanding of the cumulative effects of RHI, facilitating the identification of high risk individuals who may require surveillance to avoid prolonged exposure to RHI.